Dishevelled, a Wnt signalling component, is involved in mitotic progression in cooperation with Plk1

Dishevelled, a Wnt signalling component, is involved in mitotic progression in cooperation with Plk1
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DOI:
10.1038/emboj.2010.221
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发表时间:
2010-10-20
期刊:
影响因子:
11.4
通讯作者:
Kikuchi, Akira
Kikuchi, Akira
中科院分区:
生物学1区
文献类型:
--
作者:
Kikuchi, Koji;Niikura, Yohei;Kikuchi, Akira

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已知Wnt信号通过刺激基因表达促进G1/S进程,但这种信号是否调节有丝分裂进程尚不清楚。在此,检查了在有丝分裂中传递Wnt信号的凌乱2(Dvl 2)的功能。dvl 2在有丝分裂过程中定位于纺锤体和纺锤体极。当细胞用诺考达唑处理时,在动粒(KT)处观察到Dvl 2。Dvl 2与有丝分裂激酶Polo样激酶1(Plk 1)结合并在Thr 206处被磷酸化,并且这种磷酸化是纺锤体定向和稳定微管(MT)-KT附着所需的。Dvl 2还被发现参与纺锤体组装检查点(SAC)激酶Mps 1的激活,以及其他SAC组分Bub 1和BubR 1向KT的募集。然而,对于SAC,Plk 1对Dvl 2的磷酸化是无效的。此外,Wnt受体参与纺锤体取向,但不参与MT-KT附着或SAC。这些结果表明。Dvl 2通过Plk 1依赖和非依赖的方式调节MT+末端和SAC的动力学而参与有丝分裂进程。The EMBO Journal(2010)29,3470-3483. doi:10.1038/daj.2010.221;在线发表2010年9月7日主题分类:信号转导;细胞周期
Wnt signalling is known to promote G1/S progression through the stimulation of gene expression, but whether this signalling regulates mitotic progression is not clear. Here, the function of dishevelled 2 (Dvl2), which transmits the Wnt signal, in mitosis was examined. Dvl2 localized to the spindles and spindle poles during mitosis. When cells were treated with nocodazole, Dvl2 was observed at the kinetochores (KTs). Dvl2 bound to and was phosphorylated at Thr206 by a mitotic kinase, Polo-like kinase 1 (Plk1), and this phosphorylation was required for spindle orientation and stable microtubule (MT)-KT attachment. Dvl2 was also found to be involved in the activation of a spindle assembly checkpoint (SAC) kinase, Mps1, and the recruitment of other SAC components, Bub1 and BubR1, to the KTs. However, the phosphorylation of Dvl2 by Plk1 was dispensable for SAC. Furthermore, Wnt receptors were involved in spindle orientation, but not in MT-KT attachment or SAC. These results suggested. that Dvl2 is involved in mitotic progression by regulating the dynamics of MT plus-ends and the SAC in Plk1-dependent and -independent manners. The EMBO Journal (2010) 29, 3470-3483. doi:10.1038/emboj.2010.221; Published online 7 September 2010 Subject Categories: signal transduction; cell cycle